Direct functionalization of unactivated substrates provides an atom-economic, cost-effective, and environment-friendly methodology in product synthesis. Nitrene transfer reactions (NTRs) are one of the enabling reactions to achieve this goal. Due to its unselective nature, metal catalysts are used to control the selectivity of these NTRs, in addition to speeding up reaction rates. In this abstract, we present a joint computational and experimental study on ligand controlled chemoselective intermolecular NTRs catalyzed by silver complexes. NTRs using sulfamate-based nitrenes to substrates with both allylic C-H bonds (I) and C=C bonds (A) are tuned with I favored when tris(pyridylmethyl)amine (tpa) ligand was added to AgOTf and A favored when 4,4′,4''-Tri-tert-Butyl-2,2′:6′,2''-terpyridine (tBu3tpy) was added to AgOTf. Radical inhibition studies showed yield attenuation only when the former ligand was used. Multistate potential energy surfaces (MS-PESs) for the NTR of 2,6-difluorophenoxylsulfonylnitrene (NSO3Ar) to cyclohexene from Ag(tpa)(NSO3Ar)OTf (1N) or [Ag2tpy2(NSO3Ar)OTf]+ (2N) were investigated for both triplet (3PES) and broken symmetry singlet (BS1PES) PESs using density functional theory. The experimental chemoselectivity was qualitatively reproduced by computed transition state (TS) free energies. Analysis of the enthalpy (ΔH‡) and entropy (ΔS‡) of activation illustrated that the driving force behind the differential chemoselectivity was ΔS‡; the nitrene group in 1N is sterically hindered by the tpa ligand and OTf, hence, disfavoring aziridination. The conclusion drawn from the computations were supported by the experimental counteranion effect on the chemoselectivity. Following TSs, intermediates were found on both the 3PES and BS1PES for 1N but only on the 3PES for 2N. Products were formed directly from the BS1TSs through barrier-less rebound in the case of 2N. These different exit channels of the TSs are caused by the altered strength of the Ag–N bond between 1N and 2N, leading to their diverging tolerance to radical inhibition.

Mechanistic understanding of catalyst-controlled and tunable, chemoselective silver-catalyzed intermolecular nitrene transfers

253rd National Meeting (2017)

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